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Biomedical subjects

V Dhawan

Publications and source records attributed to V Dhawan.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effect of selecting a fixed dephosphorylation rate on the estimation of rate constants and rCMRGlu from dynamic [18F] fluorodeoxyglucose/PET data.

Several publications have discussed the estimation and physiologic significance of regional [18F]fluorodeoxyglucose (FDG) rate constants and metabolic rates. Most of these studies analyzed dynamic data collected over 45-60 min; three rate constants (k1-k3) and blood volume (Vb) were estimated and the regional cerebral metabolic rate for glucose (rCMRGlu) was subsequently derived using the measured blood glucose value and a regionally invariant value of the lumped constant (LC). The dephosphorylation rate constant (k4) was either neglected, or a fixed value was used in the estimation procedure to obtain the remaining parameters. To compare the rate constants obtained by different authors using different values of k4 is impossible without knowledge of the effect of selecting different fixed values of k4 (including zero) on the estimated rate constants and rCMRGlu. Based on our analysis of FDG/PET data from nine normal volunteer subjects, we conclude that inclusion of a fixed value for k4, in spite of a scaling effect on the absolute values of model parameters, has no effect on the coefficient of variation (CV) of within- and between-subject parameter estimates and glucose metabolic rates.

Adult↗
PubMed1988

The metabolic anatomy of paraneoplastic cerebellar degeneration.

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a "reverse cerebellar diaschisis."

Adolescent↗
PubMed1988

Effect of blood curve smearing on the accuracy of parameter estimates obtained for 82Rb/PET studies of blood-brain barrier permeability.

82Rb in conjunction with positron emission tomography (PET) has been used to estimate the blood to brain transport rate constant (K1) for Rb and the regional brain/tumour blood volume (Vb). Errors in K1 and Vb depend upon the accuracy of the measured arterial blood radioactivity and PET-monitored brain radioactivity. Arterial blood is usually sampled by placing a catheter in the radial artery and measuring the radioactivity in blood passing continuously in front of a detector or by counting discrete blood samples in a well scintillation detector. In either case, the passage of blood through catheter/pump tubing produces a smearing of the waveform as well as a delay in the arrival of radioactivity at the blood sampling site. The change in shape of the blood curve is significant for bolus-type injections and results in large errors in those model parameters which contribute substantially to the initial phase of the brain activity curve. We report here the results of computer simulations and an analysis of patient data which suggest that parameter estimation errors due to smearing and time shift may be large (greater than 50%) but that these errors can be minimised by the use of deconvolution techniques.

Blood-Brain Barrier↗
PubMed1987

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study.

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

Acute Disease↗
PubMed1987

Differences in cerebral blood flow and glucose utilization in vegetative versus locked-in patients.

Positron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked-in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 +/- 0.13 (mean +/- SEM) mg/100 gm/min, less than half the normal value of 6.82 +/- 0.23 (p less than 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked-in patients was 5.08 +/- 0.69, a 25% reduction (p less than 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain.

Adolescent↗
PubMed1987

The metabolic pathology of the AIDS dementia complex.

A progressive dementing illness, the AIDS dementia complex (ADC) is the most frequent neurological complication of the acquired immunodeficiency syndrome. Characteristic alterations in regional cerebral metabolic rate for glucose (rCMRGlc), associated with the presence or progression of ADC, were demonstrated by [18F]fluorodeoxyglucose/positron emission tomography in 9 of 12 patients with ADC compared with 18 normal volunteer subjects. In these 9 patients, two distinct patterns of regional metabolic activity were highly correlated with intersubject gray matter rCMRGlc variation and with disease severity as assessed by neuropsychological testing. Relative subcortical (thalamus and basal ganglia) hypermetabolism was characteristic of early ADC, and disease progression was accompanied by cortical and subcortical gray matter hypometabolism.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Model for 82Sr/82Rb generator elution profiles: a secondary approach to radioassay/dosimetry.

Static (dose calibrator) assays of 82Rb bolus yield erroneous estimates of administered activity by ignoring the asymmetric output of 82Sr/82Rb generators. Though on-line monitoring of elution profile improves accuracy for quantitative purposes, it requires an elaborately shielded detector and associated electronics at patient-study site. Our alternative approach based on mathematical description of the dynamic characteristics of the generator accurately predicts elution profiles over a broad range of flow rates.

Humans↗
PubMed1987

[13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors.

The biodistribution, blood clearance, and in vivo transformation of cisplatin (cisdiaminedichloroplatinum, DDP) were studied in rats using 13N-labeled and unlabeled DDP. Following the i.v. injection of [13N]DDP, virtually no 13N activity was detected in brain tissue, and no measurable amount of the 13N label was displaced from [13N]DDP. Based on these results, [13N]DDP/positron emission tomographic (PET) scans were performed in two glioblastoma patients undergoing Phase II intra-arterial (i.a.) DDP chemotherapy: [13N]DDP was infused i.v. over 13-15 min, during which time serial PET scans were obtained. One hour later, [13N]DDP mixed with cold DDP (100 mg/m2 therapeutic dose) was infused at the same rate i.a., and a second sequence of PET scans was acquired. The pharmacologic advantage of i.a. administration was calculated as the ratio of integrated tumor/brain count ratios for the i.a. and i.v. studies. Our preliminary results demonstrate the feasibility of quantifying the pharmacologic advantage of i.a. DDP chemotherapy in individual brain tumor patients using [13N]DDP and PET.

Animals↗
PubMed1986

Accuracy of PET RCBF measurements: effect of time shift between blood and brain radioactivity curves.

Analytic expressions were derived for estimating the error in PET RCBF measurements associated with the time lag between brain and blood radioactivity following bolus H2(15)O injection and during non-steady-state CO15O inhalation. This lag time reflects the physiological difference in arrival times of 15O activity at brain and radial arterial sampling site as well as the experimentally introduced resistance to flow offered by the arterial catheter/stopcock assembly. Multiple measurements of this time lag ranged between 1 and 10 s. For non-steady-state CO15O PET measurements, estimated errors in RCBF ranged from 0.02 to 30% for delays of 2-8 s and scan lengths of 30-180 s. In the range 20-100 ml min-1 per 100 g, variations in RCBF only marginally affected these errors. Errors increased with longer delays but decreased sharply with scan durations greater than 60 s. For 30-180 s scans, even larger errors are associated with the H2(15)O injection technique (peak blood activity at 10 s): 1-60% for delays of 2-8 s. A 'slow' bolus peaking at 20 s decreased the error by 40%. For the H2(15)O method it is essential to estimate the time shift to within 2 s if accurate flow measurements (error less than 5%) are to be obtained from 40-60 s scans.

Brain↗
PubMed1985

In vivo measurement of brain tumor pH using [11C]DMO and positron emission tomography.

In vivo measurements of regional brain tissue/tumor pH (rpH) have been accomplished in 9 patients with primary or metastatic brain tumors using [11C]dimethyloxazolidinedione [( 11C]DMO) and positron emission tomography. Tumor rpH values ranged from 6.88 to 7.26, whereas gray matter and white matter rpH values ranged from 6.74 to 7.09 and from 6.77 to 7.03, respectively. Our results, which are consistent with reported [14C]DMO autoradiographic measurements of brain and tumor pH, suggest that the pH microenvironment of brain tumors is not more "acidic" than that of normal gray or white matter.

Adult↗
PubMed1985

Positron emission tomographic measurement of blood-to-brain and blood-to-tumor transport of 82Rb: the effect of dexamethasone and whole-brain radiation therapy.

Unidirectional blood-to-brain and blood-to-tumor transport rate constants for rubidium 82 were determined using dynamic positron emission tomography in patients with primary or metastatic brain tumors. Regional influx rate constants (K1) and plasma water volume (Vp) were estimated from the time course of blood and brain radioactivity following a bolus injection of tracer. Eight patients were studied before and 24 to 72 hours after treatment using pharmacological doses of dexamethasone, and 6 additional patients with metastatic brain tumors were studied before and within 60 to 90 minutes after 200- to 600-rad whole-brain radiation therapy. Steroid treatment was associated with a 9 to 48% decrease in tumor K1 and a 21% mean decrease in tumor Vp. No consistent changes in K1 or Vp were observed in control brain regions. Tumor K1 and Vp did not increase in patients undergoing whole-brain radiation therapy, all of whom were taking dexamethasone at the time of study. These data suggest that corticosteroids decrease the permeability of tumor capillaries to small hydrophilic molecules (including those of some chemotherapeutic agents) and that steroid pretreatment prevents acute, and potentially dangerous, increases in tumor capillary permeability following cranial irradiation.

Adult↗
PubMed1985

Effects of xenon and krypton on regional cerebral blood flow in the rat.

The effects of high inspired concentrations of xenon and krypton on regional CBF (rCBF) were assessed in the rat using [14C]iodoantipyrine and quantitative autoradiography. Inhalation of 80% xenon for 1 or 2 min and inhalation of 40% xenon for 2 min were found to have significant effects on rCBF, including average increases of 75-96% in cerebral neocortical regions. Inhalation of 40% xenon for 1 min and of 80% krypton for 2 min had no significant effect on rCBF in most brain regions studied. If xenon inhalation produces effects on rCBF in humans similar to those observed in the rat, such effects could be an important source of error in xenon computed tomography rCBF studies.

Animals↗
PubMed1984

Accuracy of stable xenon/CT measurements of regional cerebral blood flow: effect of extrapolated estimates of brain-blood partition coefficients.

Stable xenon/computed tomographic (Xe/CT) measurements of regional brain-blood partition coefficients for xenon (lambda) and of regional cerebral blood flow (rCBF) have been reported for animal models of stroke and for patients with a variety of neurological diseases. We estimated the uncertainty in reported measurements of lambda and rCBF using computer simulations based on Kety's blood flow equation. Anesthetized baboons were scanned repeatedly for 30-60 min while inhaling an 80:20% xenon-oxygen mixture, and the resulting CT enhancement values for user-defined regions of interest were used to define a mathematical function with which to fit simulated CT enhancement data. In computer simulation studies, extrapolated and fit values of lambda for the same dataset were used to calculate rCBF, and the calculated flow values were compared. Computer simulations for heterogeneous (gray-white matter) regions indicate that better estimates of flow are obtained by fitting lambda than by using extrapolated values of lambda to calculate flow, although, paradoxically, better estimates of lambda are obtained by extrapolation than by fitting lambda.

Animals↗
PubMed1982

Mass spectrometric measurement of end-tidal xenon concentration for clinical stable xenon/computerized tomography cerebral blood flow studies.

We have demonstrated the feasibility of using a compact dedicated mass spectrometer to monitor end-tidal xenon concentration in human subjects during stable xenon computerized tomography measurements of regional cerebral blood flow. End-tidal carbon dioxide concentration is monitored simultaneously and noninvasively without degrading the dynamic response to xenon. For clinical regional cerebral blood flow studies we employed a Nuclide 3-60-G Sectorr mass spectrometer with a 3 in radius, 60 degrees magnetic sector and a variable (0-5000 V) ion accelerating potential. The required high vacuum (10(-7) Torr) was achieved and maintained by means of a turbomolecular pump. A needlemetering valve was incorporated into an anesthesia mask connector, and exhaled gases were transported to the mass spectrometer via a 6 ft length of Teflon tubing (1/16 in i.d.). Molecular flow conditions between the sample and analysis chambers were provided by use of a gold foil leak (0.0005 in. hole). At an inlet pressure of 400 m Torr (achieved by means of the needle valve), the inlet system was characterized by a gas transport lag-time of 1.3 s and a rise-time constant of 85 ms. Xenon (doubly charged ion: m/z 68) and carbon dioxide (doubly charged ion: m/z 22) were monitored alternately at 75 ms intervals. Our experience with mass spectrometry has demonstrated the feasibility of using a compact dedicated instrument for accurately and non-invasively monitoring end-tidal xenon concentration in a clinical setting.

Brain↗
PubMed1981

Lateral and third-ventricular CSF formation after metrizamide CT ventriculography.

We calculated the rates of lateral and third-ventricular (LTV) cerebrospinal fluid (CSF) formation in three patients undergoing metrizamide computed tomography (CT) ventriculography with reference to Ct estimates of ventricular volume and the time course of LTV metrizamide washout (elimination). Elimination rate constants for metrizamide were derived from measurements of LTV metrizamide concentration on serial postventriculography CT scans, and LTV volumes were estimated by partial volume analysis. CSF formation in the combined lateral ventricles averaged 0.14 ml per minute, and third-ventricular CSF formation averaged 0.014 ml per minute. Thus, the third ventricle accounted for approximately 10% of total LTV CSF production, which accords with relative weights of choroid plexus tissue in the lateral and third ventricles.

Adult↗
PubMed1979

Labeling efficiency and stomach concentration in methylene diphosphonate bone imaging.

When Tc-99m-labeled methylene diphosphonate was used 4.75 hr after reconstitution, stomach concentration was seen in the majority of patients. The number of patients with stomach concentration increases with time and is associated with the increasing amount of product breakdown. The reconstituted labeled MDP should not be used after 4-5 hr if stomach concentration is to be avoided.

Bone and Bones↗
PubMed1978

Causes and temporal sequence of onset of functional asplenia in adults.

To determine the causes and time course of onset of functional asplenia in adults, a four-part investigation was conducted. This consisted of a review of the world's literature, a survey of colleagues, a detailed study of 4,476 consecutive liver-spleen scans in three hospitals, and continued monitoring of 3,500 scans in five hospitals. Based on the findings, a classification was proposed of the causes of functional asplenia. The two major etiologies were circulatory disturbances and effects directly on splenic reticuloendothelial cells. The time course varied from the essentially instantaneous onset of functional asplenia in patients with acute splenic artery obstruction, to a prolonged and gradual onset in those with chronic damage to splenic reticuloendothelial cells. Functional asplenia was found in 0.14% of the adults who had liver-spleen scans for other indications.

Adult↗